A sigma ligand, SR 31747A, potently modulates Staphylococcal enterotoxin B-induced cytokine production in mice

Sigma receptors originally described in distinct regions of the central nervous system are expressed on cells of the immune system. A sigma ligand, SR 31747A, was observed here to inhibit in vitro the Staphylococcal enterotoxin B (SEB)-driven lymphocyte proliferation. In mice, the drug confers a potent protection against the lethality induced by SEB, stimulates the SEB-induced serum release of interleukin (IL)-10 and inhibits at the same time the systemic release of IL-2, IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6 and tumour necrosis factor-alpha (TNF-alpha). The enhancement of IL-10 production by this compound is also effective in nude mice treated with SEB, indicating that IL-10 of T-cell origin is not involved in this process. The finding that a sigma ligand protects against the SEB-induced toxicity provides insights into the clinical use of this family of compounds, particularly in food poisoning and septic shock where Staphylococcal enterotoxins are involved. The observation that this compound stimulates IL-10 synthesis indicates that it could be a potent regulatory agent of chronic inflammatory diseases.